Inhibition of asparagine synthetase effectively retards polycystic kidney disease progression.

Polycystic kidney disease (PKD) is a genetic disorder characterized by bilateral cyst formation. We showed that PKD cells and kidneys display metabolic alterations, including the Warburg effect and glutaminolysis, sustained in vitro by the enzyme asparagine synthetase (ASNS). Here, we used antisense oligonucleotides (ASO) against Asns in orthologous and slowly progressive PKD murine models and show that treatment leads to a drastic reduction of total kidney volume (measured by MRI) and a prominent rescue of renal function in the mouse.

Tree-ring oxygen isotopes record a decrease in Amazon dry season rainfall over the past 40 years.

Unlabelled: Extant climate observations suggest the dry season over large parts of the Amazon Basin has become longer and drier over recent decades. However, such possible intensification of the Amazon dry season and its underlying causes are still a matter of debate. Here we used oxygen isotope ratios in tree rings (δO) from six floodplain trees from the western Amazon to assess changes in past climate.

Violacein switches off low molecular weight tyrosine phosphatase and rewires mitochondria in colorectal cancer cells.

In the last decade, emerging evidence has shown that low molecular weight protein tyrosine phosphatase (LMWPTP) not only contributes to the progression of cancer but is associated with prostate low survival rate and colorectal cancer metastasis. We report that LMWPTP favors the glycolytic profile in some tumors. Therefore, the focus of the present study was to identify metabolic enzymes that correlate with LMWPTP expression in patient samples.

Violacein negatively modulates the colorectal cancer survival and epithelial-mesenchymal transition.

Violacein is a secondary metabolite produced by several microorganisms including Chromobacterium violaceum, and it is already used in food and cosmetics. However, due to its potent anticancer and low side effects, its molecular action needs to be deeply scrutinized. Therefore, the main objective of this study was to evaluate the violacein's ability to interfere with three cancer hallmarks: growth factors receptor-dependent signaling, proliferation, and epithelial-mesenchymal transition (EMT).

Quercetin increases mitochondrial proteins (VDAC and SDH) and downmodulates AXL and PIM-1 tyrosine kinase receptors in NRAS melanoma cells.

Melanoma is a type of skin cancer with low survival rates after it has metastasized. In order to find molecular differences that could represent targets of quercetin in anti-melanoma activity, we have chosen SKMEL-103 and SKMEL-28 melanoma cells and human melanocytes as models. Firstly, we observed that quercetin was able in reducing SKMEL-103 cell viability, but not in SKMEL-28.

Paired analysis of tree ring width and carbon isotopes indicates when controls on tropical tree growth change from light to water limitations.

Light and water availability are likely to vary over the lifespan of closed-canopy forest trees, with understory trees experiencing greater limitations to growth by light and canopy trees greater limitation due to drought. As drought and shade have opposing effects on isotope discrimination (Δ13C), paired measurement of ring width and Δ13C can potentially be used to differentiate between water and light limitations on tree growth. We tested this approach for Cedrela trees from three tropical forests in Bolivia and Mexico that differ in rainfall and canopy structure.

Colorectal Cancer Cell-Derived Small Extracellular Vesicles Educate Human Fibroblasts to Stimulate Migratory Capacity.

Colorectal cancer (CRC) is in the top 10 cancers most prevalent worldwide, affecting equally men and women. Current research on tumor-derived extracellular vesicles (EVs) suggests that these small extracellular vesicles (sEVs) play an important role in mediating cell-to-cell communication and thus potentially affecting cancer progression multiple pathways. In the present study, we hypothesized that sEVs derived from different CRC cell lines differ in their ability to reprogram normal human fibroblasts through a process called tumor education.

A comprehensive review on the role of protein tyrosine phosphatases in gastric cancer development and progression.

The main post-translational reversible modulation of proteins is phosphorylation and dephosphorylation, catalyzed by protein kinases (PKs) and protein phosphatases (PPs) which is crucial for homeostasis. Imbalance in this crosstalk can be related to diseases, including cancer. Plenty of evidence indicates that protein tyrosine phosphatases (PTPs) can act as tumor suppressors and tumor promoters.

Role of the KEAP1-NRF2 Axis in Renal Cell Carcinoma.

NRF2 is a transcription factor that coordinates the antioxidant response in many different tissues, ensuring cytoprotection from endogenous and exogenous stress stimuli. In the kidney, its function is essential in appropriate cellular response to oxidative stress, however its aberrant activation supports progression, metastasis, and resistance to therapies in renal cell carcinoma, similarly to what happens in other nonrenal cancers. While at the moment direct inhibitors of NRF2 are not available, understanding the molecular mechanisms that regulate its hyperactivation in specific tumor types is crucial as it may open new therapeutic perspectives.

Low molecular weight protein tyrosine phosphatase as signaling hub of cancer hallmarks.

In the past decade, significant progress has been made in understanding the role of protein tyrosine phosphatase as a positive regulator of tumor progression. In this scenario, our group was one of the first to report the involvement of the low molecular weight protein tyrosine phosphatase (LMWPTP or ACP1) in the process of resistance and migration of tumor cells. Later, we and others demonstrated a positive correlation between the amount of this enzyme in human tumors and the poor prognosis.

LMWPTP modulates the antioxidant response and autophagy process in human chronic myeloid leukemia cells.

In the last decade, several reports highlight the importance of the low molecular weight protein tyrosine phosphatase (LMWPTP) in cancer aggressiveness and resistance. Specifically, in chronic myeloid leukemia, we have reported that high expression of the LMWPTP maintains Src and Bcr-Abl kinases in an activated status and the glucose metabolism is directed to lactate production and, in turn, favor the pentoses pathway (one of the key process for antioxidant and protective responses). In this present study, we investigated the possible correlation between the LMWPTP and autophagy.

Italian consensus statement (2020) on return to play after lower limb muscle injury in football (soccer).

Return to play (RTP) decisions in football are currently based on expert opinion. No consensus guideline has been published to demonstrate an evidence-based decision-making process in football (soccer). Our aim was to provide a framework for evidence-based decision-making in RTP following lower limb muscle injuries sustained in football.

Ghrelin knockout mice display defective skeletal muscle regeneration and impaired satellite cell self-renewal.

Purpose: Muscle regeneration depends on satellite cells (SCs), quiescent precursors that, in consequence of injury or pathological states such as muscular dystrophies, activate, proliferate, and differentiate to repair the damaged tissue. A subset of SCs undergoes self-renewal, thus preserving the SC pool and its regenerative potential. The peptides produced by the ghrelin gene, i.

Mouse Satellite Cell Isolation and Transplantation.

Satellite cell (SC) transplantation represents a powerful strategy to investigate SC biology during muscle regeneration. We described here a protocol for SC isolation from green fluorescent protein (GFP)-expressing mice and their transplantation into murine muscles. This procedure was originally used to assess the effects of the hormone unacylated ghrelin on muscle regeneration, in particular evaluating how the increase of unacylated ghrelin in the recipient muscle affected the engraftment of donor SCs ( Reano , 2017 ).

Tree height strongly affects estimates of water-use efficiency responses to climate and CO using isotopes.

Various studies report substantial increases in intrinsic water-use efficiency (W ), estimated using carbon isotopes in tree rings, suggesting trees are gaining increasingly more carbon per unit water lost due to increases in atmospheric CO. Usually, reconstructions do not, however, correct for the effect of intrinsic developmental changes in W as trees grow larger. Here we show, by comparing W across varying tree sizes at one CO level, that ignoring such developmental effects can severely affect inferences of trees' W .

Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: Anti-inflammatory, antihistaminic, and skin barrier protection properties.

Background: Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response.

Aims: In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g).

Methods: We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient.

Unacylated Ghrelin Enhances Satellite Cell Function and Relieves the Dystrophic Phenotype in Duchenne Muscular Dystrophy mdx Model.

Muscle regeneration depends on satellite cells (SCs), quiescent precursors that, in consequence of injury or in pathological states such as muscular dystrophies, activate, proliferate, and differentiate to repair the damaged tissue. A subset of SCs undergoes self-renewal, thus preserving the SC pool and its regenerative potential. Unacylated ghrelin (UnAG) is a circulating hormone that protects muscle from atrophy, promotes myoblast differentiation, and enhances ischemia-induced muscle regeneration.

Spironolactone Prevents Endothelial Nitric Oxide Synthase Uncoupling and Vascular Dysfunction Induced by β-Adrenergic Overstimulation: Role of Perivascular Adipose Tissue.

Sustained stimulation of β-adrenoceptors (β-ARs) and activation of renin-angiotensin-aldosterone system are common features of cardiovascular diseases with rising sympathetic activation, including essential hypertension, myocardial infarction, and heart failure. In this study, we investigated the role of AT1 receptor and mineralocorticoid receptor (MR) in the vascular alterations caused by β-AR overstimulation. β-AR overstimulation with associated cardiac hypertrophy and increased vasoconstrictor response to phenylephrine in aorta were modeled in rats by 7-day isoproterenol treatment.

In vitro effects of infrared A radiation on the synthesis of MMP-1, catalase, superoxide dismutase and GADD45 alpha protein.

Harmful influences in the process of photoaging and skin damage are associated with infrared A (IRA) radiation, such as, disturbance of dermal extracellular matrix by up regulation of matrix metalloproteinase-1 (MMP1). Furthermore, DNA damage, induction of cytotoxicity and oxidative stress by decreasing natural antioxidant ability has been reported after acute exposure to IRA. The present study provides additional evidence that IRA radiation response in human skin fibroblasts produces deleterious effects to the cell, such as accelerating aging and weakening of their antioxidant defense mechanism.

Taurine supplementation reduces blood pressure and prevents endothelial dysfunction and oxidative stress in post-weaning protein-restricted rats.

Introduction: Taurine is a sulfur-containing amino acid that exerts protective effects on vascular function and structure in several models of cardiovascular diseases through its antioxidant and anti-inflammatory properties. Early protein malnutrition reprograms the cardiovascular system and is linked to hypertension in adulthood. This study assessed the effects of taurine supplementation in vascular alterations induced by protein restriction in post-weaning rats.

Bacterially mediated removal of phosphorus and cycling of nitrate and sulfate in the waste stream of a "zero-discharge" recirculating mariculture system.

Simultaneous removal of nitrogen and phosphorus by microbial biofilters has been used in a variety of water treatment systems including treatment systems in aquaculture. In this study, phosphorus, nitrate and sulfate cycling in the anaerobic loop of a zero-discharge, recirculating mariculture system was investigated using detailed geochemical measurements in the sludge layer of the digestion basin. High concentrations of nitrate and sulfate, circulating in the overlying water (∼15 mM), were removed by microbial respiration in the sludge resulting in a sulfide accumulation of up to 3 mM.

Aggressive dream content without daytime aggressiveness in REM sleep behavior disorder.

Background: REM sleep behavior disorder (RBD) is characterized by vigorous sleep motor activity associated with dream mentation. Patients with RBD frequently report action-filled and violent dreams.

Objective: To systematically assess dream characteristics and daytime aggressiveness in patients with RBD and controls.

Personality traits and metabolic control: a study in insulin-dependent diabetes mellitus patients.

Background: In the present study the authors evaluated the relationship between personality traits (according to DSM-III-R) and poor metabolic control in an adult onset insulin-dependent diabetes mellitus sample (n = 77).

Methods: Personality traits were assessed with the Personality Diagnostic Questionnaire--Revised. Metabolic control was evaluated through glycosilated hemoglobin (HbA1c): poor metabolic control was defined as HbA1c > or = 9% (normal values < 6.